This document discusses Clostridium difficile, a bacterium that causes antibiotic-associated diarrhea and colitis. It provides details on pathogenesis, risk factors, diagnostic testing, treatment of initial and recurrent infections, prevention strategies, and new treatments under investigation. Key points include the importance of the host immune response, the increasing incidence and severity of "hypervirulent" strains, challenges in treating recurrent disease, and the potential for vaccines and stool transfer therapy.
Polio: flaccid paralysis, major and minor
disease, fecal-oral
Coxsackievirus A: vesicular diseases,
meningitis; coxsackievirus B (body):
pleurodynia, myocarditis
Other echovirus and enteroviruses: like
coxsackievirus
Rhinoviruses: common cold, acid labile, does
not replicate above 33° C
Biology, Virulence, and Disease
• Small size, icosahedral capsid, positive RNA
genome with terminal protein
• Genome is sufficient for infection
• Encodes RNA-dependent RNA polymerase,
replicates in cytoplasm
Enteroviruses
• Capsid virus resistant to inactivation
• Disease due to lytic infection of important
target tissue
• Polio: cytolytic infection of motor neurons of
anterior horn and brainstem, paralysis
• Coxsackievirus A: herpangina, hand-foot-
and-mouth disease, common cold,
meningitis
• Coxsackievirus B: pleurodynia, neonatal
myocarditis, type 1 diabetes
Rhinoviruses
• Acid labile and cannot replicate at body
temperature
• Restricted to upper respiratory tract
• Common cold
Epidemiology
• Enteroviruses transmitted by fecal-oral route
and aerosols
• Rhinoviruses transmitted by aerosols and
contact
Diagnosis
• Immune assays (ELISA) or RT-PCR genome
analysis of blood, CSF, or other relevant
sample
Treatment, Prevention, and Control
• OPV and IPV polio vaccines
P
icornaviridae is one of the largest families of viruses and
includes some of the most important human and animal
viruses (Box 46-1). As the name indicates, these viruses are
small (pico) ribonucleic acid (RNA) viruses that have a
naked capsid structure. The family has more than 230
members divided into nine genera, including Enterovirus,
Rhinovirus, Hepatovirus (hepatitis A virus; discussed in
Chapter 55), Cardiovirus, and Aphthovirus. The enterovi-
ruses are distinguished from the rhinoviruses by the stabil-
ity of the capsid at pH 3, the optimum temperature
for growth, the mode of transmission, and their diseases
Multipex for viral and atypical pneumoniaPathKind Labs
Diagnosis of pneumonia can be challeging, especially if pathogens other than Streptococcus pneumoniae are involved Multiplex PCR with results available within the same day can investigate the presence or absence of 16 viruses and 5 bacteria, enablng the physician to make informed decisions about treatment, prognosis and public health and infection control measures.
Polio: flaccid paralysis, major and minor
disease, fecal-oral
Coxsackievirus A: vesicular diseases,
meningitis; coxsackievirus B (body):
pleurodynia, myocarditis
Other echovirus and enteroviruses: like
coxsackievirus
Rhinoviruses: common cold, acid labile, does
not replicate above 33° C
Biology, Virulence, and Disease
• Small size, icosahedral capsid, positive RNA
genome with terminal protein
• Genome is sufficient for infection
• Encodes RNA-dependent RNA polymerase,
replicates in cytoplasm
Enteroviruses
• Capsid virus resistant to inactivation
• Disease due to lytic infection of important
target tissue
• Polio: cytolytic infection of motor neurons of
anterior horn and brainstem, paralysis
• Coxsackievirus A: herpangina, hand-foot-
and-mouth disease, common cold,
meningitis
• Coxsackievirus B: pleurodynia, neonatal
myocarditis, type 1 diabetes
Rhinoviruses
• Acid labile and cannot replicate at body
temperature
• Restricted to upper respiratory tract
• Common cold
Epidemiology
• Enteroviruses transmitted by fecal-oral route
and aerosols
• Rhinoviruses transmitted by aerosols and
contact
Diagnosis
• Immune assays (ELISA) or RT-PCR genome
analysis of blood, CSF, or other relevant
sample
Treatment, Prevention, and Control
• OPV and IPV polio vaccines
P
icornaviridae is one of the largest families of viruses and
includes some of the most important human and animal
viruses (Box 46-1). As the name indicates, these viruses are
small (pico) ribonucleic acid (RNA) viruses that have a
naked capsid structure. The family has more than 230
members divided into nine genera, including Enterovirus,
Rhinovirus, Hepatovirus (hepatitis A virus; discussed in
Chapter 55), Cardiovirus, and Aphthovirus. The enterovi-
ruses are distinguished from the rhinoviruses by the stabil-
ity of the capsid at pH 3, the optimum temperature
for growth, the mode of transmission, and their diseases
Multipex for viral and atypical pneumoniaPathKind Labs
Diagnosis of pneumonia can be challeging, especially if pathogens other than Streptococcus pneumoniae are involved Multiplex PCR with results available within the same day can investigate the presence or absence of 16 viruses and 5 bacteria, enablng the physician to make informed decisions about treatment, prognosis and public health and infection control measures.
What are the correct probiotics to advise your ill patients to take? Should your well patients be on probiotic supplements? What doses are appropriate? Can they cause harm?
Do you know how to choose and use a probiotic properly?
Marketing has gotten out of hand, and gastroenterology professionals need to understand the oftentimes scanty data that exists on probiotic usage. Join us and learn to use this age old tool made new again.
Presented by Dr. Brecher at the 40th Annual Symposium "Diagnostic and Clinical Challenges of 20th Century Microbes", held on Nov 18, 2010 in Philadelphia.
Fecal Transplants for treatment of Clostridium Difficile, Ulcerative Colitis ...hurstm78
A summary of information about Fecal Transplants which are used to treat and effectively cure infections of anti-biotic resistant Clostridium Difficile infections of the large intestine. In addition to helping treat c. diff there have been case studies reporting success for treating Ulcerative Colitis and Crohn's Disease as well. Unfortunately access to this treatment through doctors in the United States is currently limited by FDA restrictions which require doctors to first apply for an Investigational New Drug (IND) permit. This has lead to some patients doing fecal transplants themselves.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Clostridium difficile: C. diff is more difficult than ever - presentation by J. Thomas Lamont, M.D., Harvard Medical School
1. BETH ISRAEL DEACONESS
MEDICAL CENTER
HARVARD
MEDICAL
SCHOOL
Clostridium difficile 2013:
More Difficult Than Ever
J. Thomas Lamont
2. Clostridium difficile
Spore-forming, anaerobic, gram-positive bacillus
Aslam S, et al. Lancet Infect Dis. 2005;5:549-557.
Colored transmission
electron micrograph of
C difficile forming an
endospore (red)
3. The “Difficult” Clostridium
• Discovered by Hall and O’Toole in 1935
in stools of healthy newborns
• Gram positive toxin-producing bacillus,
but harmless to infants
• Identified as cause of antibiotic
associated colitis in 1977
• Now increasing in prevalence and
severity worldwide
4. Pathogenesis of C. difficile diarrhea
Antibiotic therapy
Reduces protective colonic flora
C. difficile spores ingested
Toxins released in lumen
Diarrhea
& colitis
6. “Super C diff”: Variant Strain
• Mutated txcD gene : increased toxins
• Expression of binary toxin
• Resistant to multiple antibiotics
• Increased fecal shedding of spores
• Increased severity, death, recurrence
• Associated with epidemics
NEJM : Dec 2005
7. Pathogenesis: Role of host
immune response
• Infection elicits IgG and IgA response
• Antibodies directed at toxins
• High IgG antitoxin titer protective
• Vaccination in animals very protective
8. Serum IgG antitoxins appear during
Infantile carrier state
Are serum antitoxins protective?
Viscidi et al: J Inf Dis 1983
9. The C. difficile Carrier State
Type Prevalence Possible
Mechanism
Infants <1 yr 50-70 % Lack of toxin
receptors
Hospitalized
adults
14 % High titer serum
antitoxin
Healthy adults < 1% Barrier function of
microflora
10. A 76 yo man with resolving C
difficile…
..Is on his last day of oral metronidazole therapy for
C diff diarrhea . He has not had diarrhea for the
last five days and states that he is back to
normal. On the weekend his PCP ordered a stool
assay for C diff toxins which returns positive.
Which of these actions would you take now ?
1. Continue metro for 10 more days and re-test
2. Switch to vanco for 10 days
3. Switch to Fidaxomycin for 10 days
4. Finish metro and advise patient to call you if he
develops diarrhea
11. C diff carriage following successful Rx
Inf Control Hosp Epi Jan 2010
12. C diff Test Guidelines
• Best Bet: PCR, or screening test + PCR
• Test only unformed stools
• Do not perform a test of cure
• Correlate test results with clinical
picture
• 60-70% of healthy infants will be pos at
some time in year 1
13. Do serum antitoxins protect against C.
difficile in hospital patients receiving
Colonized by
C. difficile
84 (31%)
Hospital-acquired
28 (10%)
Hospital patients
(Acute medical ward)
LOS > 2 days
Receiving antibiotic
271 enrolled
Cases
47 (17%)
Colonized
on admission
19 (7%)
Colonized
on admission
18 (7%)
Carriers
37 (14%) Hospital-acquired
19 (7%)
antibiotics ?
540 evaluated
311 eligible
NEJM 2000;342:390
14. Serum IgG anti-toxin A levels are high
in asymptomatic carriers of C. difficile
P=0.06 P=0.002 P=0.001 P=0.005
15. C. difficile Diarrhea: Pathogenesis
Antibiotic therapy
Reduced colonic barrier flora
C. difficile ingestion & colonization
Toxins released
Effective anti-toxin
Asymptomatic Diarrhea
carriage & colitis
response
Inadequate immune
response
16. Risk of C diff with Acid Suppression
Arch Int Med 2010;170:784
18. Can I ever take antibiotics again ?
A 65 yo woman had C difficile colitis after an oral
fluoroquinilone which responded well to oral
vancomycin with cessation of diarrhea after 5 days.
She took a total of 14 days of vancomycin and now
visits your office two months later. She has had no
further diarrhea and feels well. She has two questions
Can I safely take antibiotics in the future or will I get C
diff again ?
Which antibiotics are safe for me ?
19. Second episodes of C diff ?
• Second bout years later is very rare
• Antibodies acquired in infancy or after
first bout are protective
• Choice of future antibiotics should be
based on diagnosis and culture results
• Probiotic prophylaxis during antibiotic
therapy may help
20. Recurrent C diff : a major problem
• Incidence 25-30% after succesful rx of first
attack
• Recurrent diarrhea from 2 days to 6 weeks
after stopping Met ,Vanc or Fidaxo
• Results from re-infection from spores in the
environment before the barrier flora are
reconstituted
• Multiple recurrences are common
• Responds to repeat course of M,V,F
21. 90%
21
Comparative cure and recurrence rates
Cure Rates Recurrence Rates
81.3%
72.0%
30%
20%
10%
15.4%
1. Louie et al: MEJM, 2010; 2. Results of a phase III trial comparing tolevamer, vancomycin and metronidazole in
patients with Clostridium difficile-associated diarrhea (CDAD), poster K-425a, p. 212. Abstr. 47th Intersci. Conf.
Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
70%
Metronidazole2
Vancocin2
27.1%
23.4%
0%
Metronidazole2
Vancocin2
88.2%
Fidaxomicin1
Fidaxomicin1
85.8%
Vancocin1
80%
25.3%
Vancocin1
22. Recurrent C. difficile Diarrhea
Clostridium difficile diarrhea
(n = 63)
22 (35%)
Relapsed
19 (30%)
Died
22 (35%)
Single episode
10 / 22 (45%)
Second relapse
23. Immune Immune response response to to toxin toxin A A and and protection
protection
against against C. C. difficile difficile diarrhea and and colitis
colitis
Single episode of
C. difficile diarrhea
Asymptomatic carriers
-3 1 3 6 9 12
Days after colonization
by Clostridium difficile
Adapted Adapted from from N N Engl Engl J J Med Med 2000;2000;342:342:390 390 & & Lancet Lancet 2001;2001;357:357:Serum IgG anti-Toxin A
3
2
1
Recurrent C. difficile
diarrhea
24. The best treatment of C
diff is to allow restoration
of the normal colonic
flora
The problem :
It may take up to 12
weeks !
25. Strategies for Recurrent C. difficile
• 14 day repeat course of V or Fidaxo
• Pulse-tapered 6 week course of Vanco
• Probiotics are adjunctive not primary rx
• Fidaxo (? as primary rx) to replace V,M
• Boost Immunity with C diff antibody
• Bacteriotherapy : stool transfer
• Vaccination
26. Pulsed /tapered Vancomycin for
Recurrent C. difficile
(Tedesco, 1985)
• Tapering course over six weeks
Week 1 125 mg qid
Week 2 125 mg bid
Week 3 125 mg daily
Week 4 125 mg qod
Week 5-6 125 mg q3d
• Follow above with 4 weeks cholestyramine
or probiotic
27. Protective Effects of Lactobacillus Probiotic
Placebo
n = 84
50 X109 CFU
n = 85
100 X109
CFU
n = 86
Antibiotic
Diarrhea
44.1% 28.2%
p = 0.02
15.5%
p = 0.001
C. difficile
Diarrhea
23.8% 9.4%
p = 0.03
1.2 %
p = 0.002
Am. J. Gastro 105: 1636, 2010
28. “My C diff won’t quit”
An 83 yo MD with severe CHF is awaiting
aortic valve replacement for critical AS. He
had severe C difficile infection 18 months ago
which required hospitalization. After successful
initial rx he had three severe recurrences with
fever and dehydration , all requiring
hospitalization. His cardiac team have advised
him that he cannot have his valve replaced until
the C diff is cured. He is currently on a pulsed –
tapered vanco regimen with probiotic coverage.
He previously tried IVIG and rifaxamin. He refuses
a stool transplant.
29. Chronic low dose vancocin for
multiple relapsers
• Suitable for elderly patients with
comorbidity or limited life span
• Failure of prior attempts to wean
• Recurrences are life threatening
• Not suitable for fecal transfer
• 125 mg vanco daily or qod
• Disadvantages: cost ,VRE, no trial
data
30. Severe or Fulminant C diff
• High mortality 25-35 % esp in elderly
• C diff can start mild and worsen if rx
delayed or antidiarrheals given
• Prompt dx and rx critical here
• Evidence –based rx lacking
31. Markers of Severe Infection
• WBC > 15000; fever ; dehydration
• Colonic thickening ,megacolon , ascites
• Confluent pseudomembranes
• Hemodynamic instability
• Severe abdominal distension, pain
• Elevated creatinine level
• Decreased mental status
32. Management of Fulminant Colitis
• Oral Vancomycin 500 qid or Fidaxomicin
200 mg bid ( Dificid)
• IV Metronidazole 500 q8h
• Vanco enema 500mg in 100 ml/saline
• Sub Total Colectomy for Perforation or
Megacolon
• IVIG not recommended
• Overall Mortality : 35 %
Shea Guideline: Inf Con Hosp Epi: May 2010
33. A 42 yo man had acute C diff
infection …
..that recurred twice and finally responded to a tapered pulsed regimen
of vanco followed by a two week course of S boulardii ( Florastor ).
Two weeks after cessation of therapy he had recurrence of diarrhea
and RLQ cramps with distention and gas. A C diff assay was negative
times two. His symptoms worsened and he was started on vanco
125 qid with improvement in his symptoms. After cessation of vanco
he again developed mild diarrhea 3-4 X daily , frequent passage of clear
mucus and tenesmus.
Colonoscopy and bxs are normal. Serum tTTG antibody was negative.
What would you recommend now ?
1. Stool assay for C diff
2. EGD and bx
3. UGI and SBFT
4. Rx for IBS
34. Post-infectious IBS
• IBS : 10% relate onset to infection
• GI Infection: 3-30% followed by
IBS
• Risk Factors :
– Females, age <60
– Severe infection, antibiotics
– Preexisting IBS
35. Mimics of recurrent C diff
• Post-infectious IBS
• Collagenous or microscopic colitis
• Celiac disease triggered by infection
• IBD flare with C diff infection
36. “The vanco doesn’t work anymore"
• 71 yo female with multiple bouts of C diff now
on Vanco 125 bid. Complains of 3-4 pasty
stools per day and feeling poorly. Stool test
pos for C diff toxins.
• Diarrhea while taking vanco is not due to
bacterial resistance- it doesn’t exist !
• Clinical resistance occurs in patients with
severe or fulminant disease
37. Control Of C diff in hospitals
1. Handwashing/vinyl gloves
2. Spores rest. to ethanol
3. Limit fluoroquinolone use
4. Isolate active patients
5. Role of PPIs not yet clear
38. Stool Transfer for Recurrent
C.difficile
• Rationale: Normal flora, especially
Bacteroides spp, inhibit C.difficile
• Stool donor: Healthy relative or family
member who is stool pathogen free
• Stool suspension via NJ tube,enema or
colonoscopy
• Success in open trials : cure in 144/159 pts
Am J Gastro 2000
44. C difficile :Take Home Points
• Incidence, severity and relapse rising
• Host immune response critical
• Vanco >Flagyl for severe disease
• Make sure its C diff
• Role of Fidaxomycin still unclear ($$$)
• Stool transfer when all else fails
• Vaccine development promising
Editor's Notes
Clostridium difficile is a spore-forming, anaerobic, gram-positive bacillus.1 The spores are shed by both patients and asymptomatic carriers and can persist for prolonged periods of time on environmental surfaces, including patient-care equipment.2 In addition, the spores are resistant to alcohol and most other hospital disinfectants.2 Some strains of C difficile also produce toxins, including toxins A and B, the primary virulence factors responsible for diarrhea and colitis.3
References:
1. Aslam S, et al. Lancet Infect Dis. 2005;5:549-557. 2. Dubberke ER, et al. Infect Control Hosp Epidemiol. 2008;29(Suppl 1):S81-S92. 3. Sunenshine RH, et al. Cleve Clin J Med. 2006;73:187-197.
Slide 22
A summary of potential markers of severe disease are shown. These markers have not been validated in prospective studies; however, current retrospective data suggest that these findings may be clinically useful.
rates of clinical cure with fidaxomicin were noninferior to those with vancomycin in both the modified intention-to-treat analysis (88.2% with fidaxomicin and 85.8% with vancomycin) and the per-protocol analysis (92.1% and 89.8%, respectively). Significantly fewer patients in the fidaxomicin group than in the vancomycin group had a recurrence of the infection, in both the modified intention-to-treat analysis (15.4% vs. 25.3%, P=0.005) and the per-protocol analysis (13.3% vs. 24.0%, P=0.004). The lower rate of recurrence was seen in patients with non–North American Pulsed Field type 1 strains. T